Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

Alex J. Bell; Brody H. Foy; Matthew Richardson; Amisha Singapuri; Evgeny Mirkes; Maarten van den Berge; David Kay; Chris Brightling; Alexander N. Gorban; Craig J. Galban; Salman Siddiqui

doi:10.1016/j.jaci.2019.01.014

Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

Alex J. Bell, Brody H. Foy, Matthew Richardson, Amisha Singapuri, Evgeny Mirkes, Maarten van den Berge, David Kay, Chris Brightling, Alexander N. Gorban, Craig J. Galban, Salman Siddiqui^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Asthma is a disease characterized by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood.

Objectives: We hypothesized that specific regionalization of topographical small-airway disease would best account for IOS- and MBW-measured indices in patients.

Methods: We evaluated the results of paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n = 41) and healthy (n = 11) volunteers to understand the determinants of clinical VH indices commonly reported by using IOS and MBW. Parametric response mapping (PRM) was used to calculate the functional small-airways disease marker PRMfSAD and Hounsfield unit (HU)-based density changes from total lung capacity to functional residual capacity (Delta HU); gradients of Delta HU in gravitationally perpendicular (parallel) inferior-superior (anterior-posterior) axes were quantified.

Results: The Delta HU gradient in the inferior-superior axis provided the highest level of discrimination of both acinar VH (measured by using phase 3 slope analysis of multiple-breath washout data) and resistance at 5 Hz minus resistance at 20 Hz measured by using impulse oscillometry (R5-R20) values. Patients with a high inferior-superior Delta HU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRMfSAD. A computational small-airway tree model confirmed that constriction of gravitationally dependent, lower-zone, small airway branches would promote the largest increases in R5-R20 values. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency.

Conclusions: Lower lobe predominant small-airways disease is a major driver of clinically measured VH in adults with asthma.

Original language	English
Pages (from-to)	83-93
Number of pages	11
Journal	Journal of Allergy and Clinical Immunology
Volume	144
Issue number	1
DOIs	https://doi.org/10.1016/j.jaci.2019.01.014
Publication status	Published - Jul-2019

Keywords

Asthma
computed tomography
parametric response mapping
imaging
visualization
small-airways physiology
biomarker
VENTILATION HETEROGENEITY
LUNG-FUNCTION
STANDARDIZATION
RESISTANCE
STATEMENT
PERFUSION
SCANS
COPD

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Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthmaFinal publisher's version, 8.91 MBLicence: Taverne

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Bell, A. J., Foy, B. H., Richardson, M., Singapuri, A., Mirkes, E., van den Berge, M., Kay, D., Brightling, C., Gorban, A. N., Galban, C. J., & Siddiqui, S. (2019). Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma. Journal of Allergy and Clinical Immunology, 144(1), 83-93. https://doi.org/10.1016/j.jaci.2019.01.014

@article{65bf95a91862405f8d4b14ea9e3cb587,

title = "Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma",

abstract = "Background: Asthma is a disease characterized by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood.Objectives: We hypothesized that specific regionalization of topographical small-airway disease would best account for IOS- and MBW-measured indices in patients.Methods: We evaluated the results of paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n = 41) and healthy (n = 11) volunteers to understand the determinants of clinical VH indices commonly reported by using IOS and MBW. Parametric response mapping (PRM) was used to calculate the functional small-airways disease marker PRMfSAD and Hounsfield unit (HU)-based density changes from total lung capacity to functional residual capacity (Delta HU); gradients of Delta HU in gravitationally perpendicular (parallel) inferior-superior (anterior-posterior) axes were quantified.Results: The Delta HU gradient in the inferior-superior axis provided the highest level of discrimination of both acinar VH (measured by using phase 3 slope analysis of multiple-breath washout data) and resistance at 5 Hz minus resistance at 20 Hz measured by using impulse oscillometry (R5-R20) values. Patients with a high inferior-superior Delta HU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRMfSAD. A computational small-airway tree model confirmed that constriction of gravitationally dependent, lower-zone, small airway branches would promote the largest increases in R5-R20 values. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency.Conclusions: Lower lobe predominant small-airways disease is a major driver of clinically measured VH in adults with asthma.",

keywords = "Asthma, computed tomography, parametric response mapping, imaging, visualization, small-airways physiology, biomarker, VENTILATION HETEROGENEITY, LUNG-FUNCTION, STANDARDIZATION, RESISTANCE, STATEMENT, PERFUSION, SCANS, COPD",

author = "Bell, {Alex J.} and Foy, {Brody H.} and Matthew Richardson and Amisha Singapuri and Evgeny Mirkes and {van den Berge}, Maarten and David Kay and Chris Brightling and Gorban, {Alexander N.} and Galban, {Craig J.} and Salman Siddiqui",

year = "2019",

month = jul,

doi = "10.1016/j.jaci.2019.01.014",

language = "English",

volume = "144",

pages = "83--93",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "MOSBY-ELSEVIER",

number = "1",

}

Bell, AJ, Foy, BH, Richardson, M, Singapuri, A, Mirkes, E, van den Berge, M, Kay, D, Brightling, C, Gorban, AN, Galban, CJ & Siddiqui, S 2019, 'Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma', Journal of Allergy and Clinical Immunology, vol. 144, no. 1, pp. 83-93. https://doi.org/10.1016/j.jaci.2019.01.014

TY - JOUR

T1 - Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

AU - Bell, Alex J.

AU - Foy, Brody H.

AU - Richardson, Matthew

AU - Singapuri, Amisha

AU - Mirkes, Evgeny

AU - van den Berge, Maarten

AU - Kay, David

AU - Brightling, Chris

AU - Gorban, Alexander N.

AU - Galban, Craig J.

AU - Siddiqui, Salman

PY - 2019/7

Y1 - 2019/7

N2 - Background: Asthma is a disease characterized by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood.Objectives: We hypothesized that specific regionalization of topographical small-airway disease would best account for IOS- and MBW-measured indices in patients.Methods: We evaluated the results of paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n = 41) and healthy (n = 11) volunteers to understand the determinants of clinical VH indices commonly reported by using IOS and MBW. Parametric response mapping (PRM) was used to calculate the functional small-airways disease marker PRMfSAD and Hounsfield unit (HU)-based density changes from total lung capacity to functional residual capacity (Delta HU); gradients of Delta HU in gravitationally perpendicular (parallel) inferior-superior (anterior-posterior) axes were quantified.Results: The Delta HU gradient in the inferior-superior axis provided the highest level of discrimination of both acinar VH (measured by using phase 3 slope analysis of multiple-breath washout data) and resistance at 5 Hz minus resistance at 20 Hz measured by using impulse oscillometry (R5-R20) values. Patients with a high inferior-superior Delta HU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRMfSAD. A computational small-airway tree model confirmed that constriction of gravitationally dependent, lower-zone, small airway branches would promote the largest increases in R5-R20 values. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency.Conclusions: Lower lobe predominant small-airways disease is a major driver of clinically measured VH in adults with asthma.

AB - Background: Asthma is a disease characterized by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood.Objectives: We hypothesized that specific regionalization of topographical small-airway disease would best account for IOS- and MBW-measured indices in patients.Methods: We evaluated the results of paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n = 41) and healthy (n = 11) volunteers to understand the determinants of clinical VH indices commonly reported by using IOS and MBW. Parametric response mapping (PRM) was used to calculate the functional small-airways disease marker PRMfSAD and Hounsfield unit (HU)-based density changes from total lung capacity to functional residual capacity (Delta HU); gradients of Delta HU in gravitationally perpendicular (parallel) inferior-superior (anterior-posterior) axes were quantified.Results: The Delta HU gradient in the inferior-superior axis provided the highest level of discrimination of both acinar VH (measured by using phase 3 slope analysis of multiple-breath washout data) and resistance at 5 Hz minus resistance at 20 Hz measured by using impulse oscillometry (R5-R20) values. Patients with a high inferior-superior Delta HU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRMfSAD. A computational small-airway tree model confirmed that constriction of gravitationally dependent, lower-zone, small airway branches would promote the largest increases in R5-R20 values. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency.Conclusions: Lower lobe predominant small-airways disease is a major driver of clinically measured VH in adults with asthma.

KW - Asthma

KW - computed tomography

KW - parametric response mapping

KW - imaging

KW - visualization

KW - small-airways physiology

KW - biomarker

KW - VENTILATION HETEROGENEITY

KW - LUNG-FUNCTION

KW - STANDARDIZATION

KW - RESISTANCE

KW - STATEMENT

KW - PERFUSION

KW - SCANS

KW - COPD

U2 - 10.1016/j.jaci.2019.01.014

DO - 10.1016/j.jaci.2019.01.014

M3 - Article

SN - 0091-6749

VL - 144

SP - 83

EP - 93

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 1

ER -

Functional CT imaging for identification of the spatial determinants of small-airways disease in adults with asthma

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Keywords

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